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The short version:
Diane (Naomi watts) moves to Hollywood after winning a jitterbug dance contest. She goes to auditions, meets and eventually falls in love with "Rita". Rita doesn't feel the same and starts dating Adam Kesher (the director). Diane is a shitty actress and can't land any roles. Between this and her unrequited love, she slips into depression.

Eventually Diane is invited to a dinner party where she learns Rita and Adam are engaged. She snaps. She hires a hitman to kill Rita. He does and she regrets it and goes off the deep end.

The bulk of the movie is a dream. In this dream she is Betty, a successful actress that can get any part she wants. She didn't get the part in the Olivia North story (the part Rita got in real life) is because there is a mob conspiracy to get this other girl the part. Also in her dream her and Rita are in love and her life is perfect. They finally go to club silencio where she learns nothing is real. At this point she realizes she's dreaming this perfect life.

The only part I'm not to clear on is if she is dreaming this, wakes up, then kills herself, or she is dreaming this in the instant she is dying, (her fake perfect life flashing before her eyes).

Starts in reality, then goes into a dream world where she populates said dream with people from real life (look closely at the dinner party, everyone from the dream world is there, but in a different role).

I guess I should've been less specific with that. There's tons of "it was all a dream" movies, but wizard of oz is the most well know and least risk of spoilers. Plus lynch is a huge fan of oz (check out wild at heart for all thing oz and lynch)

I think she's just dead in the car, her deteriorating brain is making her last dream really confusing/terrifying. She starts off as herself, then becomes Naomi watts because she forgets what she looks like, but still sees different parts of her life in third person. Her brain is very deteriorated by the time the old people (maybe her parents?) start ganging up on her, so she decides to end it all.

Mulholland Drive is simply David Lynch's dressed up version of a porno. Why are you even paying attention to the story, just watch the damn thing! Thats what Mr. Lynch would suggest anyway; everything there is to know about the movie is right there on the screen, nothing more, nothing less. A confused new girl in town, a struggling director with creepy overbearing producers breathing down his neck telling him which 'actress' to cast, a wife two timing him with the pool guy, oversexed washed up actors reliving their better days at the mercy of young girls who want to make it in hollywood, A COWBOY... the list of goes on. I've made my point. Watch it again.